The existing diagnostic criteria for Dementia with Lewy bodies (DLB) has been criticized for being inadequate at differentiating DLB from Alzheimer's disease (AD). The main focus of this grant is to improve the differential diagnosis of DLB relative to AD, and to better understand the neuropathologic underpinnings of DLB and predictors of decline. Specifically, we will determine whether the addition of vigilance and visual tasks improves our ability to distinguish DLB from AD. We will also expand on our prior findings of daytime drowsiness in DLB, by investigating whether DLB and not AD, is associated with disturbed sleep/wake mechanisms based on indices from polysomnography and multiple sleep latency tests. Neuropathologic analyses will help to determine whether our diagnostic accuracy shows improvement when REM sleep behavior disorder (RBD) and excessive daytime sleepiness are included as diagnostic features. In addition, the contribution of Lewy body, Lewy neurite and AD pathology will be examined in relation to clinical/cognitive presentation and rate of disease progression. A secondary focus of the grant is to characterize preclinical predictors of DLB by analyzing data from persons who convert from a diagnosis of Mild Cognitive Impairment (MCI) to dementia in the Mayo Alzheimer's Disease Patient Registry (ADPR) and Alzheimers' Disease Research Center (ADRC) (Mayo African American Normative Studies and Minority/Indigent program). We hypothesize that non-amnestic MCI (with visual and/or attention/executive dysfunction) and RBD will be predictive of subsequent progression to DLB and not AD. The overarching theme of this grant application is to improve the early detection and diagnostic accuracy of DLB. This has implications for symptom management, development of treatment options and for providing education and support to DLB patients and their caregivers.